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At least 19 records

Early Unloading After ACL Rupture and Prior to Surgical Restabilization in Mice Slows Post-Traumatic Osteoarthritis Progression

Purpose: People who sustain joint injuries such as anterior cruciate ligament (ACL) rupture often go on to develop post-traumatic osteoarthritis (PTOA). ACL injuries are often treated with ACL reconstruction, but there is typically a gap of several weeks between injury and surgery. However, it is unclear how loading or unloading of the injured joint during the early postinjury period affects the progression of PTOA. The goal of this study was to determine how unloading between noninvasive ACL injury and surgical restabilization of the injured joint affects PTOA progression in mice. Findings: Mice were subjected to noninvasive ACL injury or no injury followed by 1 week of hindlimb unloading (HLU) or normal cage activity. After 1 week of HLU or cage activity, mice underwent restabilization surgery or no surgery. ACL injury resulted in considerable epiphyseal trabecular bone loss regardless of HLU or cage activity. HLU groups exhibited significantly reduced chondrophyte/osteophyte formation, OA scoring, and synovitis at day 42. Single-cell RNA sequencing revealed that 1 week of HLU resulted in more neutrophils and less monocytes-macrophages in the injured joint. Conclusions: This study establishes that 1 week of HLU after ACL injury effectively slowed PTOA progression, suggesting that the early inflammatory response and joint instability play a key role in PTOA initiation and progression, and neutrophils and monocytes-macrophages play roles in the modulation. However, subsequent joint restabilization surgery caused greater inflammatory protease activity in the joint and exacerbated the loss of epiphyseal trabecular bone but did not significantly diminish OA score or synovitis.

ACL injury↗

Integration of polyurethane meniscus scaffold during ACL revision is not reliable at 5 years despite favourable clinical outcome

Abstract Purpose The aim of this study was to evaluate the clinical outcome at 5‐year follow‐up of a one‐step procedure combining anterior cruciate ligament (ACL) reconstruction and partial meniscus replacement using a polyurethane scaffold for the treatment of symptomatic patients with previously failed ACL reconstruction and partial medial meniscectomy. Moreover, the implanted scaffolds have been evaluated by MRI protocol in terms of morphology, volume, and signal intensity. Methods Twenty patients with symptomatic knee laxity after failed ACL reconstruction and partial medial meniscectomy underwent ACL revision combined with polyurethane‐based meniscal scaffold implant. Clinical assessment at 2‐ and 5‐year follow‐ups included VAS, Tegner Activity Score, International Knee Documentation Committee (IKDC), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the Lysholm Score. MRI evaluation of the scaffold was performed according to the Genovese scale with quantification of the scaffold’s volume at 1‐ and 5‐year follow‐ups. Results All scores revealed clinical improvement as compared with the preoperative values at the 2‐ and 5‐year follow‐ups. However, a slight, but significant reduction of scores was observed between 2 and 5 years. Concerning the MRI assessment, a significant reduction of the scaffold’s volume was observed between 1 and 5 years. Genovese Morphology classification at 5 years included two complete resorptions (Type 3) and all the remaining patients had irregular morphology (Type 2). With regard to the Genovese Signal at the 5‐year follow‐up, three were classified as markedly hyperintense (Type 1), 15 as slightly hyperintense (Type 2), and two as isointense (Type 1). Conclusion Simultaneous ACL reconstruction and partial meniscus replacement using a polyurethane scaffold provides favourable clinical outcomes in the treatment of symptomatic patients with previously failed ACL reconstruction and partial medial meniscectomy at 5 years. However, MRI evaluation suggests that integration of the scaffold is not consistent. Level of evidence Level IV.

Pereira, Hélder↗

Estimating IDP Origins Using ACLED Political Violence Events: Validation with Lebanon IDP Flow Data

A key input in modeling population distribution and flows following conflict events is the inclusion of Internally Displaced Person (IDP) flows between administrative units within a country. These flows are critical for capturing population movement and redistribution driven by current events, particularly conflict. In some cases, IDP destination data are available while origin data is incomplete or unavailable. This creates a gap in understanding where displacement is occurring, limiting the ability to model population redistribution accurately. Without origin data, it is not possible to reallocate population flows or accurately represent where displacement is occurring within the country. This report evaluates whether Armed Conflict Location Event Data (ACLED) political violence event data can be used to estimate IDP origin distributions when direct origin data are unavailable. The approach is validated using historical IDP flow data from Lebanon, where both origins and destinations are observed. Results show that ACLED event distributions strongly correspond to observed IDP-origin patterns, particularly when using cumulative 60-day event windows. The method is most reliable for identifying major origin districts and approximating proportional origin shares. However, it is not intended to reconstruct exact individual displacement flows, but rather to provide a probabilistic spatial allocation of displacement origins.

99 GENERAL AND MISCELLANEOUS↗

B332 & B151 ACL Events

In September 2019, two Unexpected Radiological Event (HP-FO-601) reports were submitted to document the exceedance of a worker's default Administrative Control Level (ACL) of 100 mrem/y. One involved work in B332; the second in B151. B332 event: The worker was new to B332 and had completed qualification as an Associate Fissile Material Handler (FMH) in April of 2019. The worker received 61 mrem in June and an additional 100 mrem in July. The worker was on a monthly TLD exchange cycle. B151 event: A PLS radiochemist received ~20 mrem for the 1st quarter of the year and ~120 mrem for the 2nd quarter of the year. The worker was on a quarterly TLD exchange cycle.

61 RADIATION PROTECTION AND DOSIMETRY↗

Cytosolic Acetyl-CoA Generated by ATP-Citrate Lyase Is Essential for Acetylation of Cell Wall Polysaccharides

Abstract Plant cell wall polysaccharides, including xylan, glucomannan, xyloglucan and pectin, are often acetylated. Although a number of acetyltransferases responsible for the acetylation of some of these polysaccharides have been biochemically characterized, little is known about the source of acetyl donors and how acetyl donors are translocated into the Golgi, where these polysaccharides are synthesized. In this report, we investigated roles of ATP-citrate lyase (ACL) that generates cytosolic acetyl-CoA in cell wall polysaccharide acetylation and effects of simultaneous mutations of four Reduced Wall Acetylation (RWA) genes on acetyl-CoA transport into the Golgi in Arabidopsis thaliana. Expression analyses of genes involved in the generation of acetyl-CoA in different subcellular compartments showed that the expression of several ACL genes responsible for cytosolic acetyl-CoA synthesis was elevated in interfascicular fiber cells and induced by secondary wall-associated transcriptional activators. Simultaneous downregulation of the expression of ACL genes was demonstrated to result in a substantial decrease in the degree of xylan acetylation and a severe alteration in secondary wall structure in xylem vessels. In addition, the degree of acetylation of other cell wall polysaccharides, including glucomannan, xyloglucan and pectin, was also reduced. Moreover, Golgi-enriched membrane vesicles isolated from the rwa1/2/3/4 quadruple mutant were found to exhibit a drastic reduction in acetyl-CoA transport activity compared with the wild type. These findings indicate that cytosolic acetyl-CoA generated by ACL is essential for cell wall polysaccharide acetylation and RWAs are required for its transport from the cytosol into the Golgi.

Cell Biology↗

Effects of 9.5 Years of Whole-Soil Warming on the Fatty Acid and n-Alkanes Composition in Bulk Soil and Density Fractions at Blodgett Experimental Forest, California, USA

Original data of molecular data (fatty acids and n-alkanes) including concentrations and calculated molecular proxies in a whole-soil warming experiment at the Blodgett Forest Research Station after 9.5 years of warming. The study site has a Mediterranean climate with annual average temperature of 12.5 ℃ and annual average precipitation of 1774 mm. The study site is characterized by a mesic Ultic Alfisol formed from granitic parent material, corresponding to a Dystric Cambisol under the World Reference Base for Soil Resources (WRB) classification system. Experimental warming is applied throughout the soil profile to a depth of 1 m using vertically embedded heating cables that raise soil temperature by 4 °C relative to ambient conditions. Soil samples were collected on 1 May 2023, after the experiment had been operating continuously for about 9.5 years since its initiation in January 2014.The data has been processed from raw data and cross-validated by other peers. The dataset includes: - Bulk_Fattyacid_9.5-year_Soil_Warming_Blodgett, California, USA: fatty acid concentrations and proxies including Carbon Preference Index (CPI) and Average Chain Length (ACL) of bulk soil organic carbon; - Fractions_Fattyacid_9.5-year_Soil_Warming_Blodgett, California, USA: fatty acid concentrations and proxies including CPI and ACL of free particulate organic matter (fPOM) and mineral-associated organic matter (MAOM); - Bulk_Alkanes_9.5-year_Soil_Warming_Blodgett, California, USA: n-alkanes concentrations and proxies including CPI and ACL of bulk soil organic carbon; - Fractions_Alkanes_9.5-year_Soil_Warming_Blodgett, California, USA: n-alkanes concentrations and proxies including CPI and ACL of fPOM and MAOM; - n-Alkanes_All_Monomer_Concentration_9.5-year_Soil_Warming_Blodgett, California, USA: concentration of all the n-alkane monomers identified and integrated for bulk soil, fPOM and MAOM; - Fattyacid_All_Monomer_Concentration_9.5-year_Soil_Warming_Blodgett, California, USA: concentration of all the fatty acid monomers including diacids identified and integrated for bulk soil, fPOM, and MAOM. All data are provided in CSV format and can be viewed using Microsoft Excel. We specifically look at fatty acids (FA) and n-alkanes in bulk soil, fPOM and MAOM and calculated molecular proxies such as CPI and ACL to understand the source of oragnic carbon (with ACL) and degree of decomposition (CPI) of each soil fraction. Due to lack of long-chain fatty acids (carbon number ⩾ 20), microorganism-derived organic carbon is characterized by shorter ACL in comparison to plant-derived organic carbon. Fresh SOC is characterized by even-over-odd dominance for fatty acids and odd-over-even dominance for n-alkanes. Therefore, CPI indicates whether soil organic carbon (SOC) represents fresh input (CPI > 10) or is strongly decomposed (close to 1). The research questions should be then, after 9.5-year warming: 1. whether the relative contribution between microorganism-derived and plant-derived SOC in each soil fraction? 2. whether fPOM became more decomposed whereas MAOM remained relatively persistent in each soil fraction across the soil depth?

Carbon↗

Plant wax and carbon isotope response to heat and drought in the conifer Juniperus monosperma

Plant waxes, including n-alkanes, are commonly used for a wide range of paleo-applications. Several common traits of n-alkanes that are used as paleo-proxies include chain length distribution and average chain length (ACL), as well as plant wax carbon and hydrogen isotopic compositions. The effect of climate on plant wax traits has been the subject of many studies, but a common challenge with modern calibrations is disentangling the effects of species (genetic), temperature, and precipitation from one another. Here, in this study, we explore the effect of temperature and drought, independently and combined, on plant wax composition of the species Juniper monosperma in a large ecosystem-scale field manipulation experiment. We find that n-alkane concentrations significantly increase with temperature, but other parameters (including ACL) are not affected. These results support physiological studies that identify n-alkanes as an important barrier to water loss within the plant cuticle. Combined with prior studies, it appears that changes in ACL within sediments are likely controlled by changes in species composition rather than directly by changes in climate. We find little variation in the carbon isotopic composition (δ 13 C) of n-alkanes across the treatments whereas bulk leaf δ 13 C values are higher in the heat and drought treatment. Because leaf δ 13 C values represent a weighted C assimilation signal, these values reflect differences in leaf gas exchange among treatments, whereas the n-alkanes are synthesized when water availability is higher and differences among treatments are not significant enough to influence their values. These results have important implications for using n-alkane traits, including ACL and δ 13 C values, for paleoenvironmental reconstructions.

Compound-specific isotope analysis↗

“Figure‐of‐Eight” Suture‐Button Technique for Fixation of Displaced Anterior Cruciate Ligament Avulsion Fracture

Objective To assess the clinical results of the “figure‐of‐eight” suture‐button technique in the arthroscopic treatment of anterior cruciate ligament (ACL) tibial avulsion fractures. Methods This was a retrospective study reviewing data from September 2013 to June 2019. A total of 27 patients (13 males and 14 females) who underwent arthroscopic “figure‐of‐eight” suture‐button fixation for displaced ACL avulsion fractures were analyzed. The mean age of the patients in the sample was 15.8 years (10–29 years), with a mean follow‐up of 24 months (6–48 months). According to Meyers–McKeever classification, 11 patients were classified as type III and 16 as type IV. All patients were evaluated following the guidelines of the radiological union, the Lysholm knee scoring scale, and the International Knee Documentation Committee (IKDC). Results Fractures were united within 3 months after surgery in all 27 cases. During the last follow‐up, all the anterior drawer and Lachman tests were negative, except in 1 patient whose anterior drawer test was 1° positive. The range of motion was improved from 72.22° ± 27.92° before surgery to 137.78° ± 7.38° at the last follow‐up ( P < 0.05); the Lysholm score was improved from 45.81 ± 10.94 before surgery to 93.04 ± 5.66 at the last follow‐up ( P < 0.05); and the IKDC score was increased from 43.89 ± 11.16 before surgery to 90.26 ± 5.86 at the last follow‐up ( P < 0.05). In 1 patient, an inflammatory reaction was observed at the medial incision of the tibial tubercle; the symptoms disappeared with administration of antibiotics for 1 week. All patients returned to their preinjury physical activities at the last follow‐up. Conclusion The “figure‐of‐eight” suture‐button technique achieves a satisfactory clinical outcome and provides an effective method for the treatment of displaced ACL avulsion fractures.

Kuang, Shi‐da↗

Single-cell RNA-Seq reveals changes in immune landscape in post-traumatic osteoarthritis

Osteoarthritis (OA) is the most common joint disease, affecting over 300 million people world-wide. Accumulating evidence attests to the important roles of the immune system in OA pathogenesis. Understanding the role of various immune cells in joint degeneration or joint repair after injury is vital for improving therapeutic strategies for treating OA. Post-traumatic osteoarthritis (PTOA) develops in ~50% of individuals who have experienced an articular trauma like an anterior cruciate ligament (ACL) rupture. Here, using the high resolution of single-cell RNA sequencing, we delineated the temporal dynamics of immune cell accumulation in the mouse knee joint after ACL rupture. Our study identified multiple immune cell types in the joint including neutrophils, monocytes, macrophages, B cells, T cells, NK cells and dendritic cells. Monocytes and macrophage populations showed the most dramatic changes after injury. Further characterization of monocytes and macrophages reveled 9 major subtypes with unique transcriptomics signatures, including a tissue resident Lyve1 hi Folr2 hi macrophage population and Trem2 hi Fcrls + recruited macrophages, both showing enrichment for phagocytic genes and growth factors such as Igf1 , Pdgfa and Pdgfc. We also identified several genes induced or repressed after ACL injury in a cell type-specific manner. This study provides new insight into PTOA-associated changes in the immune microenvironment and highlights macrophage subtypes that may play a role in joint repair after injury.

60 APPLIED LIFE SCIENCES↗

A highly-selective chloride microelectrode based on a mercuracarborand anion carrier

The chloride gradient plays an important role in regulating cell volume, membrane potential, pH, secretion, and the reversal potential of inhibitory glycine and GABAA receptors. Measurement of intracellular chloride activity, $a^i_{Cl}$, using liquid membrane ion-selective microelectrodes (ISM), however, has been limited by the physiochemical properties of Cl - ionophores which have caused poor stability, drift, sluggish response times, and interference from other biologically relevant anions. Most importantly, intracellular $HCO^-_3$ may be up to 4 times more abundant than Cl - (e.g. skeletal muscle) which places severe constraints on the required selectivity of a Cl - - sensing ISM. Previously, a sensitive and highly-selective Cl - sensor was developed in a polymeric membrane electrode using a trinuclear Hg(II) complex containing carborane-based ligands, [9]-mercuracarborand-3, or MC3 for short. Here, we have adapted the use of the MC3 anion carrier in a liquid membrane ion-selective microelectrode and show the MC3-ISM has a linear Nernstian response over a wide range of a Cl (0.1 mM to 100 mM), is highly selective for Cl - over other biological anions or inhibitors of Cl - transport, and has a 10% to 90% settling time of 3 sec. Importantly, over the physiological range of aCl (1 mM to 100 mM) the potentiometric response of the MC3-ISM is insensitive to $HCO^-_3$ or changes in pH. Finally, we demonstrate the biological application of an MC3-ISM by measuring intracellular aCl, and the response to an external Cl-free challenge, for an isolated skeletal muscle fiber.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Disruption of the Snf1 Gene Enhances Cell Growth and Reduces the Metabolic Burden in Cellulase-Expressing and Lipid-Accumulating Yarrowia lipolytica

Yarrowia lipolytica is known to be capable of metabolizing glucose and accumulating lipids intracellularly; however, it lacks the cellulolytic enzymes needed to break down cellulosic biomass directly. To develop Y. lipolytica as a consolidated bioprocessing (CBP) microorganism, we previously expressed the heterologous CBH I, CBH II, and EG II cellulase enzymes both individually and collectively in this microorganism. We concluded that the coexpression of these cellulases resulted in a metabolic drain on the host cells leading to reduced cell growth and lipid accumulation. The current study aims to build a new cellulase coexpressing platform to overcome these hinderances by (1) knocking out the sucrose non-fermenting 1 ( Snf1 ) gene that represses the energetically expensive lipid and protein biosynthesis processes, and (2) knocking in the cellulase cassette fused with the recyclable selection marker URA3 gene in the background of a lipid-accumulating Y. lipolytica strain overexpressing ATP citrate lyase ( ACL ) and diacylglycerol acyltransferase 1 ( DGA1 ) genes. We have achieved a homologous recombination insertion rate of 58% for integrating the cellulases- URA3 construct at the disrupted Snf1 site in the genome of host cells. Importantly, we observed that the disruption of the Snf1 gene promoted cell growth and lipid accumulation and lowered the cellular saturated fatty acid level and the saturated to unsaturated fatty acid ratio significantly in the transformant YL163t that coexpresses cellulases. The result suggests a lower endoplasmic reticulum stress in YL163t, in comparison with its parent strain Po1g ACL-DGA1. Furthermore, transformant YL163t increased in vitro cellulolytic activity by 30%, whereas the “total in vivo newly formed FAME (fatty acid methyl esters)” increased by 16% in comparison with a random integrative cellulase-expressing Y. lipolytica mutant in the same YNB-Avicel medium. The Snf1 disruption platform demonstrated in this study provides a potent tool for the further development of Y. lipolytica as a robust host for the expression of cellulases and other commercially important proteins.

09 BIOMASS FUELS↗

Equilibration and “Thermalization” in the Adapted Caldeira–Leggett Model

I explore the processes of equilibration exhibited by the Adapted Caldeira–Leggett (ACL) model, a small unitary “toy model” developed for numerical studies of quantum decoherence between an SHO and an environment. I demonstrate how dephasing allows equilibration to occur in a wide variety of situations. While the finite model size and other “unphysical” aspects prevent the notions of temperature and thermalization from being generally applicable, certain primitive aspects of thermalization can be realized for particular parameter values. I link the observed behaviors to intrinsic properties of the global energy eigenstates, and argue that the phenomena I observe contain elements which might be key ingredients that lead to ergodic behavior in larger more realistic systems. The motivations for this work range from curiosity about phenomena observed in earlier calculations with the ACL model to much larger questions related to the nature of equilibrium, thermalization, and the emergence of physical laws.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Effect of High-Protein Diets on Integrated Myofibrillar Protein Synthesis before Anterior Cruciate Ligament Reconstruction: A Randomized Controlled Pilot Study

Increasing dietary protein intake during periods of muscle disuse may mitigate the resulting decline in muscle protein synthesis (MPS). The purpose of this randomized pilot study was to determine the effect of increased protein intake during periods of disuse before anterior cruciate ligament (ACL) reconstruction on myofibrillar protein synthesis (MyoPS), and proteolytic and myogenic gene expression. Six healthy, young males (30 ± 9 y) were randomized to consume a high-quality, optimal protein diet (OP; 1.9 g·kg−1·d−1) or adequate protein diet (AP; 1.2 g·kg−1·d−1) for two weeks before ACL reconstruction. Muscle biopsies collected during surgery were used to measure integrated MyoPS during the intervention (via daily deuterium oxide ingestion) and gene expression at the time of surgery. MyoPS tended to be higher, with a large effect size in OP compared to AP (0.71 ± 0.1 and 0.54 ± 0.1%·d−1; p = 0.076; g = 1.56). Markers of proteolysis and myogenesis were not different between groups (p > 0.05); however, participants with greater MyoPS exhibited lower levels of MuRF1 gene expression compared to those with lower MyoPS (r = −0.82, p = 0.047). The data from this pilot study reveal a potential stimulatory effect of increased daily protein intake on MyoPS during injury-mediated disuse conditions that warrants further investigation.

Howard, Emily E. (ORCID:0000000179791236)↗

Designing a Site Closure Strategy for Uranium in Groundwater and Surface Water - 19534

A site closure strategy was designed and mapped for residual uranium present in groundwater and surface water at the US DOE Office of Legacy Management (LM) Monticello Mill Tailings Site (MMTS) Operable Unit (OU) III, which is regulated under CERCLA. The MMTS is a former mill site that was used to process uranium and vanadium ore in southeastern Utah until 1960. OU III includes surface water in Montezuma Creek and groundwater present in a shallow alluvial aquifer along the creek valley for several kilometers downgradient of the former mill site. The current remedy consists of an operating pump-and-treat system, monitored natural attenuation (MNA), and institutional controls (ICs). Performance evaluations indicate that a prolonged restoration period is likely, as well as an asymptotic trend in uranium concentrations that still exceed the remediation goal. Multiple strategies and scenarios were evaluated before selecting a preferred site closure strategy. Recommendations were developed to support advancing the site towards closure over the next few years and guide the process of regulatory interactions and decision making at the MMTS OU III. Site closure is an important milestone that reflects successful remedial progress at LM sites. Post-closure site management would be maintained to ensure conditions are protective of human health and the environment. The site closure strategy was considered in the context of site remedial progress. The primary sources of groundwater contamination have been removed, including mill tailings and contaminated soils, sediment, and debris. Five-year reviews have regularly concluded that the remedy is protective of human health and environment and that ICs are effective in preventing exposure to contaminated groundwater. The affected aquifer is low-yielding and has no history of domestic use. In 2004, the final remedy selected in the Record of Decision (ROD) was MNA with ICs. However, a pump-and-treat system was installed and continues to operate as a contingency remedy in the area with the highest residual uranium concentrations. The need for a contingency pump-and-treat system was triggered by a departure of the long-term monitoring data from model projections that were used as the basis for remedy performance metrics specified in the ROD. In 2015, the pump-and-treat system was expanded. Average uranium concentrations have declined locally over time. However, monitoring data and column studies indicate that the system effectiveness will eventually become ineffective in reducing uranium concentrations, likely due to the reequilibration of uranium present in the solid matrix in various states (i.e., sorbed, precipitated). Currently, there are no agreed-upon metrics for discontinuing the contingency pump-and-treat system. Three closure strategies effectively applied at other CERCLA sites were considered at MMTS OU III: (1) restoring natural attenuation conditions and conducting MNA; (2) applying alternate concentration limits (ACLs); and (3) waiving a remedial goal based on technical impracticability (TI). Each closure strategy was evaluated in the following manner: (1) identifying the criteria and requirements associated with current regulations, policy, and guidance, (2) assessing the ability to meet those criteria based on the current site knowledge and the conceptual site model, and (3) identifying data gaps that need to be filled to further assess the closure strategy. Following this evaluation, a preferred closure strategy was selected: to transition to a remedy based on MNA and maintenance of ICs, without active remediation. Several scenarios for transitioning to the preferred closure strategy were identified. Each scenario consisted of 'if/then logic' associated with a larger decision diagram. The decision diagram considered the current conceptual site model (CSM) and potential outcomes of studies that will be conducted to fill data gaps, as well as the performance of the existing treatment system and long-term monitoring data. Two scenarios for transitioning to the preferred closure strategy were highlighted for future planning and were described in detail. For both scenarios, the preferred closure strategy includes demonstrating criteria for MNA acceptance, pump-and-treat termination, long-term monitoring, and eventual site delisting. Recommended actions over the next few years were also developed, including updating the CSM, conducting numerical modeling to predict remedial performance and time frames, conducting geochemical analyses to assess uranium fate and transport, and summarizing the lines of evidence and basis for MNA. This detailed example of the development of a site-specific closure strategy provides the thought process and decision logic used to assess uncertainty using an if/then framework; identify common elements and recommended actions to advance the site towards closure; and navigate the inherent uncertainty in the timing of future events, outcome of regulatory discussions, and remedial progress over time that is common to many complex US DOE facilities. In addition, the national regulations, policy, guidance, and state of practice regarding commonly used site closure strategies was summarized for consideration, including MNA, ACLs, and TI. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Uranium Mill Tailings Radiation Control Act Title II DOE Due Diligence and Lessons Learned from a Previous Site Transfer - 20352

Title II of the Uranium Mill Tailings Radiation Control Act (UMTRCA) established that a government agency will provide perpetual care for closed uranium and thorium ore-processing sites that were operating under an NRC source material license in 1978 or were licensed thereafter. Commercial owners (licensees) operating under an NRC or agreement state specific license when UMTRCA was passed are responsible for conducting reclamation of any byproduct material remaining from uranium-ore processing operations in accordance with an NRC or agreement state approved reclamation plan. Reclamation includes both surface and groundwater remedies. Upon completion of reclamation and approval by NRC, the site is required to be transferred to either the host state or the DOE for long-term surveillance and maintenance. Since UMTRCA's enactment, six Title II sites have been transferred to DOE; an additional 24 Title II sites are anticipated to be transferred before 2050. DoE's role mandated under UMTRCA Title II as the long-term care custodian is to perform 'monitoring, maintenance, and emergency measures necessary to protect the public health and safety.' UMTRCA requires that the licensee pay a long-term surveillance charge 'sufficient to cover the annual costs of site surveillance.' However, at some sites such as the Bluewater, New Mexico, Disposal Site, this mandate has required additional effort and expense by DOE, beyond the originally anticipated and intended scope within UMTRCA, but within the authority of DOE under UMTRCA. In 1997, the Bluewater site became the second UMTRCA Title II site to be transferred to DOE. The site was the location of a uranium mill operated from 1953 until 1982. The specific licensee began site reclamation in 1991, and by 1995 all tailings and contaminated materials were encapsulated in two tailings disposal cells and other disposal areas. In addition to surface contamination, milling activities impacted groundwater in the two upper aquifers. In 1989, the specific licensee attempted active groundwater remediation; however, no significant reduction in contaminant concentrations was observed. As a result, the specific licensee applied to NRC for alternate concentration limits (ACLs) in 1990, which were approved in 1996 as being protective, after additional corrective actions were performed. Since transfer of the Bluewater site to DOE, unforeseen challenges have occurred, requiring additional actions. The first challenge is the occurrence of surface depressions located on the northern section of the main tailings disposal cell. The depressions were first observed during DoE's initial inspection in 1998; however, evidence of these can be observed on satellite images taken prior to transfer. Since being first observed, the depressions have continued to grow both in depth and areal extent. Due to the design of the main tailings disposal cell, the depressions impede storm water from being effectively shed off the 101- hectare (250-acre) top slope of the main tailings disposal cell. Instead, storm water accumulates in the depressions, forming a large ephemeral pond that has stored up to 16.3 x 10{sup 6} liters (4.3 million gallons) of stormwater. The ponding poses a potential risk to the integrity of the main tailings disposal cell in the case of a large storm event, with the potential to cause the pond to overtop and erode the cover material and underlying waste. DOE has taken a number of short-term actions to monitor, measure, and reduce the ponding and is currently working with the US Army Corps of Engineers to design and construct a repair. Additional challenges are associated with groundwater at the Bluewater site. Nine wells were present on the 1335-hectare (3300-acre) site upon transfer. Groundwater compliance was called into question after the State of New Mexico reduced its uranium groundwater standard from 5.0 to 0.03 milligrams per liter in 2004, and when an ACL for uranium was exceeded in a site monitoring well in 2010. Acquiring historical groundwater data and subsequent evaluations as well as additional DOE groundwater monitoring led to installing 10 new monitoring wells and performing additional site hydrogeology recharacterization. DOE continues to evaluate groundwater conditions at the site and works with the NRC to determine regulatory requirements and a path forward. As a result of lessons learned at the Bluewater site and other Title II sites, improved processes have been implemented at a programmatic level to increase due diligence before site transfer and prevent similar issues from occurring at other UMTRCA Title II sites under long-term management. DoE's due diligence process is documented in the Process for Transition of UMTRCA Title II Disposal Sites to DOE for Long-Term Surveillance and Maintenance and is designed to ensure that DOE has no technical or compliance concerns with regulatory decisions that might compromise protectiveness following site transfer to DOE. Implementation of the due diligence process has increased DoE's role prior to site transfer and has been effective in identifying potential issues. Actions by NRC and specific licensees, in response to enhanced due diligence efforts by DOE, are expected to minimize, if not totally prevent, the need for unanticipated actions by DOE pertaining to the surface and groundwater remedies after site transfer. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Antibiotic Treatment Prior to Injury Abrogates the Detrimental Effects of LPS in STR/ort Mice Susceptible to Osteoarthritis Development

Post traumatic osteoarthritis (PTOA) is a form of secondary osteoarthritis (OA) that develops in ~50% of cases of severe articular joint injuries and leads to chronic and progressive degradation of articular cartilage and other joint tissues. PTOA progression can be exacerbated by repeated injury and systemic inflammation. Few studies have examined approaches for blunting or slowing down PTOA progression with emphasis on systemic inflammation; most arthritis studies focused on the immune system have been in the context of rheumatoid arthritis. To examine how the gut microbiome affects systemic inflammation during PTOA development, we used a chronic antibiotic treatment regimen starting at weaning for 6 weeks before anterior cruciate ligament (ACL) rupture in STR/ort mice combined with lipopolysaccharide (LPS)-induced systemic inflammation. STR/ort mice develop spontaneous OA as well as a more severe PTOA phenotype than C57Bl/6J mice. By 6 weeks post injury, histological examination showed a more robust cartilage staining in the antibiotic-treated (AB) STR/ort mice than in the untreated STR/ort controls. Furthermore, we also examined the effects of AB treatment on systemic inflammation and found that the effects of LPS administration before injury are also blunted by AB treatment in STR/ort mice. The AB- or AB+LPS-treated STR/ort injured joints more closely resembled the C57Bl/6J VEH OA phenotypes than the vehicle- or LPS-treated STR/ort, suggesting that antibiotic treatment has the potential to slow disease progression and should be further explored therapeutically as prophylactic post injury.

60 APPLIED LIFE SCIENCES↗

Effect of Background Electrolyte Composition on the Interfacial Formation of Th(IV) Nanoparticles on the Muscovite (001) Basal Plane

Understanding the impact of actinide nanoparticle (NP) formation is important to assess radionuclide mobility in the environment. We combined surface X-ray diffraction (SXRD) and in situ AFM to investigate the previously reported unusual electrolyte effects on Th uptake on mica. At low [Th] (0.1 mM), interfacial structures show a broad Th electron density (~50 Å). A linear decrease of Th uptake with decreasing hydration enthalpy of the electrolyte cation (Li+, K+, NH4+, and Cs+) indicates a competitive effect between Th and the electrolyte cation. Na+ is a clear outlier from this trend. In situ AFM imaging confirms the results. Particles show a vertical size of ~1–2 nm and larger lateral dimensions of ~10–20 nm, which is typical for particles formed at interfaces (heterogeneous nucleation). At high [Th] = 1 and 3 mM, all investigated electrolytes (ACl, A = Li+, Na+, K+) show similar Th uptake, indicating a much smaller impact of electrolyte composition. The interfacial structures are dominated by a high Th loading at a distinct distance (~6.5 Å) from the surface. Therefore, the main retention mechanism at high [Th] is suggested to be the sorption of Th NPs aggregated from Th oligomers present in solution (homogeneous nucleation).

Neumann, J↗